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WHAT FUTURE FOR RIBAVIRIN

ROLE OF RIBAVIRIN IN HCV TREATMENT MECHANISM OF ACTION. Guanosine analogInhibits inosine 5' monophosphate dehydrogenaseReduces intracellular guanosine stores Reduces RNA replicationModulates immune response by altering cytokine synthesis and cytotoxic T cell responseIncorporated into viral RNA

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WHAT FUTURE FOR RIBAVIRIN

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    2. WHAT FUTURE FOR RIBAVIRIN? Mitchell L Shiffman, MD Chief, Hepatology Section Medical Director, Liver Transplant Program Virginia Commonwealth University Medical Center Richmond, VA

    3. ROLE OF RIBAVIRIN IN HCV TREATMENT MECHANISM OF ACTION Guanosine analog Inhibits inosine 5’ monophosphate dehydrogenase Reduces intracellular guanosine stores Reduces RNA replication Modulates immune response by altering cytokine synthesis and cytotoxic T cell response Incorporated into viral RNA leading to extensive mutagenesis

    4. TREATMENT OF CHRONIC HCV OPTIMIZING SVR The ability to achieve SVR is the result of three independent steps: Achieving a virologic response 2. Maintaining the virologic response 3. Not relapsing Ribavirin plays a role in all 3 of these steps. Side effects lead to dose reduction and/or discontinuation of treatment in 10-40% of patients.

    5. ROLE OF RIBAVIRIN IN HCV TREATMENT ENHANCES VIROLOGIC RESPONSE

    6. ROLE OF RIBAVIRIN IN HCV TREATMENT SPECTRUM OF RESPONSES

    7. ROLE OF RIBAVIRIN IN HCV TREATMENT ENHANCES COMPLETE EVR

    8. ROLE OF RIBAVIRIN IN HCV TREATMENT REDUCES RELAPSE

    9. TREATMENT OF CHRONIC HCV EXTENDING RIBAVIRIN TREATMENT

    10. ROLE OF RIBAVIRIN IN HCV TREATMENT IMPACT OF RIBAVIRIN DOSE

    11. ROLE OF RIBAVIRIN IN HCV TREATMENT HIGHER DOSES REDUCE RELAPSE

    13. HIGH DOSE RIBAVIRIN AND EPOETIN VIROLOGIC RESPONSE

    14. TREATMENT OF CHRONIC HCV IMPACT OF STOPPING RIBAVIRIN

    15. ROLE OF RIBAVIRIN IN HCV TREATMENT IMPACT OF STOPPING RIBAVIRIN

    16. ROLE OF RIBAVIRIN ON HCV TREATMENT IMPACT OF DOSE REDUCTION

    18. TELAPREVIR - PROVE 2 PHASE 2 FINAL RESULTS

    19. TELAPREVIR - PROVE 3 NON-RESPONDER RETREATMENT

    20. ROLE OF RIBAVIRIN ON HCV TREATMENT WHAT WILL THE FUTURE BE?

    21. ROLE OF RIBAVIRIN IN HCV TREATMENT SUMMARY Ribavirin is an essential component of HCV treatment: Enhances response Prevents breakthrough Reduces relapse Higher starting doses of ribavirin are associated with lower relapse and higher SVR rates Stopping ribavirin prematurely is associated with breakthrough and a higher relapse rate. Reducing the dose of ribavirin has particularly after the patient has become HCV RNA undetectable has minimal impact on SVR.

    22. RIBAVIRIN AND HCV TREATMENT WHAT IS THE FUTURE Replacing ribavirin even with a potent protease inhibitor appear to: Reduce virologic response Increases relapse Additional studies to remove ribavirin from the HCV treatment paradigm will be explored when several protease and/or polymerase inhibitors are available. It may be more realistic to remove peginterferon as opposed to ribavirin in the future.

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